Infection of Human immunodeficiency viruses (HIV includes HIV-1 and HIV-2)/Acquired immunodeficiency syndrome (AIDS) is a globe pandemic. HIV-1 and HIV-2 are retroviruses and human pathogens. They infect 38.6 million people worldwide. (UNAIDS. 2006 report on the global AIDS epidemic, ISBN 92 9 173511 6) In the United States, 1,039,000 to 1,185,000 people suffer from HIV infection, and the cumulative number of diagnoses of Acquired Immunodeficiency Syndrome (AIDS) patients through 2004 is 944,305. (CDC HIV/AIDS Surveillance Report: HIV Infection and AIDS in the United States, 2004).
HIV/AIDS is a major health problem in developing countries. Although HIV/AIDS epidemic is under control and the number of new AIDS patients has been stabilized in some developed countries since late 1990s, mainly due to education and antiretroviral treatments, HIV infection spreads quickly in many developing areas, such as in countries in Africa, east and southeast Asia. The new cases of HIV infection grow exponentially, threatening millions of lives in these regions. In some area, HIV infects a quart of the local population. That not only reduces the life expectancy of the population but also destroys social structure of these affected countries, undermining the stability of the region.
Treatment of HIV/AIDS has been an avid research topic since the discovery of HIV viruses in the early 80s. There are drugs available to treat HIV-1 infection. The Food and Drug Administration (FDA) approved the first antiretroviral drug, AZT, in 1987. Currently, twenty FDA-approved antiretroviral drugs and their combinations are available for treating HIV-1 infection. These drugs target different stages of viral replication. For example, Enfuvirtide (T20) is an attachment inhibitor which prevents HIV virus from fusing with T cell membrane, therefore, blocks HIV's entry to its target cell. Nucleoside reverse transcriptase inhibitors (NRTIs) are a group of drugs that inhibit reverse transcriptase, blocking the enzyme's function of copying viral RNA to DNA during HIV's reverse transcription. A well-known representative of NRTIs is zidovudine (AZT). Protease inhibitors (PIs) have been developed to disrupt formations of enzymes and structural proteins of HIV by inhibiting HIV protease. They block the HIV in protein glycosylation phase, rendering the HIV noninfectious. Another group of drugs are non-nucleoside reverse transcriptase inhibitors (NNRTIs) that also inhibit reverse transcriptase by binding to it and blocking the enzyme's function of synthesize viral DNA in the HIV reverse transcription phase.
Antiretroviral cocktails are combinations of antiretroviral drugs. By using these cocktail, doctors are able to reduce the HIV viral load to a very low level in peripheral blood of treated AIDS patients and relieve the symptoms of AIDS in these patients, meanwhile reduce the side effects of the antiretroviral drugs. These treatments successfully prolong the lives of AIDS patients.
Drug resistance of HIV is a major challenge in treatments of HIV infection and AIDS. Although these drug mentioned above show considerable effect on slowing down viral replication during treatments, emerging strains of HIV that are resistant to existing drugs continue to be one of the biggest challenges in effectively treating HIV infection. Quite a number of patients fail their antiretroviral therapies because of emerging of drug resistant strains of HIV. Emerging of the drug-resistant strains is due to the natural selection and the rapid turnover of HIV during the course of infection that contributes a high viral mutation rate makes the virus easy to escape the conventional antiviral treatment. Under these circumstances, incomplete viral suppression caused by insufficient drug potency, poor compliance and intrinsic pharmacological barriers provides fertile ground for drug-resistant strains to emerge, undermining the therapeutic management of HIV disease. Therefore, finding new therapeutic methods and targets has never been as important as it is now.